Figure 3.

Inactivation of tumor suppressor genes via KRAS/PI3K/PTEN/AKT. The KRAS oncogene is considered the most frequent mutation in the pancreatic tumorigenesis process observed in pancreatic adenocarcinoma (PanIN-1) and is involved in signal transduction of an important cell signaling pathway, the PI3K/PTEN/AKT pathway. KRAS encodes the Ras protein through a small GTPase-binding protein. Active RAS is promoted by guanine nucleotide exchange factors (GEFs) in response to stimulation of a cell surface receptor, epidermal growth factor receptor (EGFR, a member of the human tyrosine kinase epidermal receptor family), resulting in the recruitment of PI3K. PI3K will form PIP2 (phosphatidylinositol 4,5-bisphosphate) and then PIP3 (phosphatidylinositol 4,5-triphosphate. The second messenger PIP3 recruits AKT (serine/threonine kinase) and PDK1 (phosphoinositide-dependent kinase 1 to the membrane). AKT affects various signaling pathways, such as the mTOR pathway, which regulates nutrient, oxygen, and energy levels in cells and the NF-κB pathway (nuclear factor kappa B). PTEN is responsible for regulating the intensity of PI3K and, consequently, its effects on the intracellular signal transduction cascade. PTEN deficiency or absence causes hyperactivity of the PI3K pathway, due to the accumulation of PIP3, leading to the appearance of high degrees of neoplastic transformations. From: Author.